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Hereditary hemochromatosis
Richard S Ajioka1, James P Kushner
1Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Seminars in Hematology
|October 17, 2002
Summary
Hereditary hemochromatosis (hh) is an iron overload disorder caused by HFE gene mutations. Clinical penetrance of liver damage in homozygotes ranges from 4-25%, necessitating continued screening and management.
Area of Science:
- Genetics
- Gastroenterology
- Internal Medicine
Background:
- Hereditary hemochromatosis (hh) is an autosomal recessive disorder of iron metabolism.
- It is caused by mutations in the HFE gene, most commonly the C282Y mutation.
- The HFE protein regulates dietary iron absorption by enterocytes.
Purpose of the Study:
- To review studies on hereditary hemochromatosis that avoid ascertainment bias.
- To clarify the clinical penetrance of organ damage in individuals with hh.
- To provide guidance on screening and management of hh.
Main Methods:
- Review of studies attempting to avoid ascertainment bias in hereditary hemochromatosis.
- Focus on biopsy-proven hepatic fibrosis and/or cirrhosis as a criterion for morbidity.
- Analysis of existing data to estimate clinical penetrance.
Main Results:
- Clinical penetrance of hh-related morbidity (hepatic fibrosis/cirrhosis) in homozygotes ranges from 4% to 25%.
- Ascertainment bias in previous studies led to wide discrepancies in reported prevalence of organ damage.
- Elevated transferrin saturation is a common laboratory finding in hh.
Conclusions:
- The clinical penetrance of hereditary hemochromatosis is narrower than previously suggested but still requires clarification.
- Continued screening for hemochromatosis in primary care is pragmatic.
- Maintaining serum ferritin levels below approximately 100 μg/L with phlebotomy is recommended for management.